June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
MIF targeted neuroprotection through human serum albumin nanoparticle drug delivery
Tyler Heisler-Taylor; Sumaya Hamadmad; Dena Martini; Yushin Jeng; Katelyn E Swindle-Reilly; Kasey Hill; Mitch Phelps; Colleen M Cebulla
Author Affiliations & Notes
  • Tyler Heisler-Taylor
    Ophthalmology and Visual Sciences, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Sumaya Hamadmad
    Ophthalmology and Visual Sciences, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Dena Martini
    Ophthalmology and Visual Sciences, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Yushin Jeng
    Ophthalmology and Visual Sciences, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Katelyn E Swindle-Reilly
    Biomedical Engineering, The Ohio State University, Columbus, Ohio, United States
    Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio, United States
  • Kasey Hill
    CCC - Sponsored Research, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Mitch Phelps
    College of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Colleen M Cebulla
    Ophthalmology and Visual Sciences, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Footnotes
    Commercial Relationships   Tyler Heisler-Taylor None; Sumaya Hamadmad None; Dena Martini None; Yushin Jeng None; Katelyn Swindle-Reilly Vitranu, Code C (Consultant/Contractor), Vitranu, Code I (Personal Financial Interest), Vitranu, Code P (Patent); Kasey Hill None; Mitch Phelps None; Colleen Cebulla None
  • Footnotes
    Support  VSRCP core grant P30EY032857 The Ohio Lions Eye Research Foundation (OLERF) This work was supported by The Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense, through the FY17 Vision Research Program, Technology/Therapeutic Development Award under Award No. W81XWH1810805. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. OSUMC Shared Resource Core Grant P30CA016058
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 2626. doi:
  • Views
  • Share
  • Tools
    • Alerts
      User Alerts
      You are adding an alert for:
      MIF targeted neuroprotection through human serum albumin nanoparticle drug delivery
      You will receive an email whenever this article is corrected, updated, or cited in the literature. You can manage this and all other alerts in My Account
      The alert will be sent to:
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation
      Citation

      Tyler Heisler-Taylor, Sumaya Hamadmad, Dena Martini, Yushin Jeng, Katelyn E Swindle-Reilly, Kasey Hill, Mitch Phelps, Colleen M Cebulla; MIF targeted neuroprotection through human serum albumin nanoparticle drug delivery. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2626.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

      ×
    • Get Permissions
  • Supplements
Abstract

Purpose : Nanoparticles are becoming increasingly popular as a method to enhance drug delivery. We seek to utilize human serum albumin (HSA) and hyaluronic acid (HA) to develop nanoparticles to deliver a small molecule macrophage migration inhibitory factor (MIF) inhibitor ibudilast to treat N-methyl-D-aspartate (NMDA) excitotoxic retinal damage in chicks.

Methods : Blank and ibudilast loaded HSA nanoparticles with or without HA coating were produced and characterized with dynamic light scattering (DLS) and TEM. ARPE-19 cells were used to assess nanoparticle cellular distribution with confocal and toxicity with MTT and TUNEL assay. Under an IACUC approved protocol, in vivo experiments were performed in white leghorn chicks (n=39). NMDA (500 nmol) + nanoparticles (20µl total volume) were injected into the left eye while the right eye received nanoparticles and vehicle (sterile saline). Chicks were sacrificed at either one day post-injection (D1) or seven days post-injection (D7). Cell death was determined via TUNEL assay at D1 and nanoparticle distribution was assessed at D1 and D7.

Results : Nanoparticles closely matched the established literature in size, charge (zeta potential), and TEM morphology. Ibudilast concentration was measured as 0.0027mg/ml via LC-MS/MS. Nanoparticles were found to adhere to ARPE-19 cells. Both in vitro and in vivo experiments showed no cellular or retinal toxicity due to the nanoparticles. Two patterns were found in chick eyes; in undamaged eyes nanoparticles aggregated on the inner limiting membrane, while in damaged eyes they were found distributed across the retina. There was a 75% reduction in cell death due to ibudilast loaded HSA nanoparticles in NMDA damaged eyes compared to NMDA controls (740.8±323.9 cells/mm2 vs. 2900.1±865.5 cells/mm2, p = 0.0356).

Conclusions : This study shows preliminary data establishing the potential therapeutic benefits of nanoparticle-based drug delivery of MIF inhibition to treat excitotoxic damage. Additional experiments will be required to optimize the nanoparticle design and drug absorption.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Attribution-NonCommercial-NoDerivatives
Copyright © 2024 Association for Research in Vision and Ophthalmology.
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×
This site uses cookies. By continuing to use our website, you are agreeing to our privacy policy.Accept